Masa Hayase

Role of K+ Channels in Regulating Spontaneous Activity in Detrusor Smooth Muscle In Situ in the Mouse Bladder

PURPOSE We investigated the functional role of K(+) channels for regulating spontaneous activity in mouse bladder detrusor smooth muscle. MATERIALS AND METHODS The effects of different K(+) channels blockers on spontaneous changes in membrane potential and intracellular Ca(2+) dynamics were examined using intracellular recording techniques and Ca(2+) imaging with fluo-4 fluorescence, respectively. RESULTS Detrusor smooth muscle generated spontaneous action potentials and Ca(2+) transients. Iberiotoxin (0.1 microM), charybdotoxin (0.1 microM) or tetraethylammonium (1 mM) increased the amplitude of action potentials and prolonged their repolarizing phase without inhibiting their after-hyperpolarization. Tetraethylammonium (10 mM) but not stromatoxin (0.1 microM) suppressed after-hyperpolarization and further increased the amplitude and half duration of action potentials. Apamin (0.1 microM) increased the frequency of action potentials but had no effect on their configuration. Spontaneous Ca(2+) transients were generated in individual detrusor smooth muscle cells and occasionally propagated to neighboring cells to form intercellular Ca(2+) waves. Transmural nerve stimulations invariably initiated synchronous Ca(2+) transients within and across muscle bundles. Charybdotoxin (0.1 microM) increased the amplitude of spontaneous Ca(2+) transients, while the subsequent application of tetraethylammonium (10 mM) increased their half duration. In addition, tetraethylammonium increased the synchronicity of Ca(2+) transients in muscle bundles. CONCLUSIONS These results suggest that large and intermediate conductance Ca(2+) activated K(+) channels contribute to action potential repolarization and restrict the excitability of detrusor smooth muscle in the mouse bladder. In addition, the activation of voltage dependent K(+) channels is involved in repolarization and after-hyperpolarization, and it has a fundamental role in stabilizing detrusor smooth muscle excitability.

Expression of α1-Adrenoceptor Subtype mRNA as a Predictor of the Efficacy of Subtype Selective α1-Adrenoceptor Antagonists in the Management of Benign Prostatic Hyperplasia

PURPOSE We examined the correlation between the expression of alpha1-adrenoceptor subtype mRNA in the prostate and the clinical efficacy of subtype selective alpha1-adrenoceptor antagonists. We discuss the possibility of individualizing drug therapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS A total of 33 patients randomized to the tamsulosin group and 28 randomized to the naftopidil group were enrolled in this study. Each group of patients was administered 0.2 mg tamsulosin hydrochloride or 50 mg naftopidil daily for 12 weeks. Four prostate needle biopsy specimens were obtained from the transition zone to examine the expression of alpha-adrenoceptor subtypes. Specimens were stored at -80 C until used for TaqMan quantitative reverse transcriptase-polymerase chain reaction, which was performed after 12 weeks of treatment. RESULTS Based on the results of quantitative reverse transcriptase-polymerase chain reaction the tamsulosin and naftopidil groups were grouped into alpha1a-adrenoceptor dominant (22 and 12 patients) and alpha1d-adrenoceptor dominant (11 and 16, respectively) subgroups. The efficacy of tamsulosin hydrochloride and naftopidil differed depending on the dominant expression of the alpha1-adrenoceptor subtype in the prostate. Tamsulosin hydrochloride was more effective in patients with dominant expression of the alpha1a-adrenoceptor subtype, whereas naftopidil was more effective in those with dominant expression of the alpha1d-adrenoceptor subtype. CONCLUSIONS The expression level of alpha1-adrenoceptor subtype mRNA in the prostate could be a predictor of the efficacy of subtype selective alpha1-adrenoceptor antagonists in patients with benign prostatic hyperplasia. This result implies that genetic differences are responsible for the diverse responses to these drugs.

Effects of imatinib mesylate on spontaneous electrical and mechanical activity in smooth muscle of the guinea-pig stomach

Effects of imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, on spontaneous activity of interstitial cells of Cajal (ICC) and smooth muscles in the stomach were investigated.

Evolving mechanisms of action of alverine citrate on phasic smooth muscles.

We have investigated the mechanisms underlying the paradoxical ability of the antispasmodic, alverine, to enhance spontaneous activity in smooth muscles while suppressing evoked activity.

Pseudo-clitoromegaly associated with congenital prepubic sinus

Abstract  We operated on a 12‐year‐old girl who had clitoromegaly and a sinus on the midline prepubic area congenitally. The prepubic sinus appeared to point to the clitoris on the preoperative magnetic resonance image, but the relation between the sinus and clitoromegaly was unclear. Gray‐brown discharge was emitted at the site of dissection between the prepuce and clitoris and the size of the clitoris became normal. The sinus was excised, revealing a tract 1.5 cm long that extended to the retropubic sinus, and ended in a fibrous tract that was linked to the clitoris. This suggested pseudo‐hypertrophy because of the discharge collected in the end of the prepubic sinus.

EXPRESSION LEVEL AND ROLE IN URETERAL CONTRACTION OF ALPHA1-ADRENOCEPTOR SUBTYPES IN HUMAN URETER

Hypothesis / aims of study Recently there have been some reports that tamsulosin is effective for discharge of ureter stones. The relation between voiding function of the lower urinary tract and alpha1-adrenoceptor (AR) is well known, and is applied clinically. On the other hand, there has been little research into alpha1-AR of the upper urinary tract. We studied the expression and role in ureteral contraction of alpha1-AR subtypes, which was considered to clarify the mechanism of ureteral urodymanics and passing ureter stones.

Primary pure carcinoid tumour of the testis: A case report and review of the literature

Primary testicular carcinoid tumours (TCT) are very rare, and a large tumour size and the presence of carcinoid syndrome predict a malignant course. Histologically, it is difficult to differentiate between benign and malignant TCTs. We report a case of a primary pure TCT with an unusual presentation in a 23- year-old man, who had an asymptomatic, enlarged scrotum on the right side for 7 years. On gross examination, the tumour was 9.6 cm in diameter. The Ki-67 labelling index was 19.8%. High inguinal orchidectomy was performed, and 30 months after surgery the patient remains asymptomatic.

ALTERED DISTRIBUTION OF INTERSTITIAL CELLS IN THE GUINEA PIG BLADDER FOLLOWING BLADDER OUTLET OBSTRUCTION

AIMS We investigated the effects of bladder outlet obstruction (BOO) on the distribution of interstitial cells (ICs) in the guinea-pig bladder. METHODS Bladder overactivity of BOO animals was validated with urodynamic studies. Immunohistochemical analyses for Kit and vimentin as markers for ICs were performed on both BOO and control bladders. Morphological and functional properties of detrusor smooth muscle (DSM) were examined with alpha-smooth muscle actin staining and intracellular recording, respectively. Electron microscopy was also carried out to characterize ultrastructural morphology of ICs. RESULTS Two weeks after surgery, BOO animals showed an increased voiding frequency and a reduced voiding volume. Filling cystometry demonstrated a frequent incidence of non-voiding contractions, a reduced interval between voiding contractions and an increased voiding pressure in BOO bladders. In BOO bladders, the thickness of suburothelial and subserosal connective tissue layers was increased, whilst that of detrusor smooth muscle (DSM) layer was less affected. Population of Kit or vimentin immunoreactive ICs was increased in subserosal layers, and their distribution was altered in suburotherial layer in BOO bladders. Neither alpha-actin immunoreactivity nor spontaneous electrical activity of DSM was altered in BOO bladders. ICs were characterized by their numerous mitochondria and caveolae, and had a close contact with each other and with neighboring DSM or nerves. CONCLUSIONS These results demonstrated the increased population of ICs in the BOO guinea-pig model for the first time, and suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity.